Paul Levine, a resident of West Tisbury, former professor at Harvard, and visiting professor at Stanford University, writes occasionally about scientific research taking place today, along with profiles of the Islands scientists and their work and facts of scientific note on the Island. This week, he follows up on his gene-editing column from six weeks ago, which described the genetics research that has led to CRISPR, which stands for clustered regularly interspaced short palindromic repeats. If youre wondering what that is, read on.
In this, the second column on the subject of gene editing, imagine a world in which many human genetic disorders have been eliminated, no children are born with cystic fibrosis, Tay-Sachs disease, sickle cell anemia, or other genetic disorders. Welcome to the world of CRISPR, an acronym for clustered regularly interspaced short palindromic repeats of the DNA of a gene. CRISPR can locate a defective gene and, along with an enzyme called Cas9, can, like a pair of scissors, snip out the unwanted gene and suture a desirable gene in its place. It is a technique of genetic editing that is more precise, efficient, and affordable than anything that has come before. What I describe below is specific to the Vineyard (the elimination of Lyme disease) and relevant to society as a whole for the potential for great good, but also for possible misuse use of the technology, which has raised questions of ethics and safety.
CRISPR-Cas9 as a tool for genetic editing has a history that goes back to a 2011 scientific conference at which microbiologist Emmanuelle Charpentier, now the director of the Max Planck Institute for Infection Biology in Berlin, met Jennifer Doudna, professor of chemistry and molecular and cell biology at the University of California, Berkeley. They talked about CRISPR-Cas9, and what follows is the story of one of the most significant achievements in genetics since the discovery of the structure and function of DNA. It is a story that involves brilliant scientists, competition, big egos, patent disputes, and the possibility of a Nobel Prize, not to mention the immense financial gain by biotech, agribusiness, and pharmaceutical companies.
Prior to todays application of CRISPR to edit genes, it was known that it was a means by which bacteria protected themselves from infection by viruses by recognizing and binding to viral DNA and destroying it with enzymes. Charpentier and Doudna wondered whether the technique could be applied to other things than the detection and destruction of viral DNA. If it could, it might lead to a way to snip out bad genes and possibly replace them with good ones. They began a collaborative research project with bacteria, and developed a technique for cutting out and replacing bacterial genes with CRISPR and an enzyme, Cas9. In other words, it was now possible to edit the bacterial genome by cutting and pasting genes. Doudna and Charpentier published their research in the journal Science in 2012. Aware of the great potential that the ability to edit genomes presented, the University of California patented their discovery.
At about the same time, Feng Zhang at the Broad Institute of MIT and Harvard was working with Cas9, and discovered that CRISPR-Cas9 could also be applied to edit the genes of animals and plants. His discovery was published a few months after the publication of the work of Doudna and Charpentier.
The Broad Institute applied for and received a patent based on the results of Zhangs research. However, prior to their filing, the University of California, Berkeley, had filed for and received a patent based on Doudnas and Charpentiers research.
In a patent dispute, it was ruled that the Broad Institutes patent took precedent over the University of California patent because it applies to animal and plant cells. The University of California, Berkeley, has asserted that although their patent involves bacteria, it includes all forms of life.
Unfortunately, a consequence of the dispute is the enmity that has developed between some of the parties involved.
It was not long before life scientists throughout the world began to develop the technique in order to advance progress in human genetic engineering to cure some of the 6,000 human genetic disorders.
With respect to applications of CRISPR-Cas9 to edit human genes, research is underway to use it to control insect- and spider-borne disease; for example, mosquitoes that carry the malaria parasite and the viruses that cause dengue, West Nile, and Zika fever. The object of the research is to produce sterile female mosquitoes by using CRISPR-Cas9 to edit out the genes required for their fertility, and distribute the sterile females in areas around the world where mosquito-borne diseases occur. This approach has been met with some success at the laboratory level.
Another research effort which might be familiar to you is to eliminate Lyme disease by distributing white-footed mice that have been manipulated with gene-editing techniques to effectively be immune to the bacteria which causes Lyme, all using CRISPR-Cas9. This would break the transmission cycle of the bacteria (see MV Times, Scientist proposes genetic attack on M.V. ticks, July 20, 2016).
I havent mentioned possible commercial applications of CRISPR-Cas9, and the great profits to be made by Monsanto and other agribusiness companies by the production of genetically modified plants and domestic animals. The technology is also appealing to Big Pharma. Its worth looking at the highly controversial and ethical questions that accompany the use of CRISPR-Cas9. In contrast with noninheritable somatic cell human gene editing described above, there is another technique called germ line gene editing, which makes gene changes at the level of human eggs, sperm, and embryos that would be heritable. Experiments on human embryos have been carried out by scientists in China and the U.K. that have raised concern that CRISPR-Cas9 could lead to the production of designer babies parents choosing the traits they want their children to have. Designer babies are a vast topic, too vast to bring up here, but there is an excellent discussion of the subject in Roger Gosdens The Brave New World of Reproductive Technology.
Jennifer Doudna, at U.C. Berkeley, and Feng Zhang at MIT, the principal developers and promoters of gene editing, appear to be at odds over the ethical questions surrounding the technology. Doudna is concerned with the ethics and the publics perception of CRISPR-Cas9, but Zhang appears less so, and prefers to drive the research to cure genetic disorders, putting aside the possibility of the production of designer babies.
If you want to explore CRISPR-Cas9 and come to an opinion regarding one of the most significant developments in genetics in this century, I urge you to read Robert Kolkers 2016 article in Bloomberg BusinessWeek, How Jennifer Doudnas Gene Editing Technique Will Change the World. It can be found at bit.ly/CRISPRdoudna. Listen to Doudnas TED Talk here: bit.ly/TEDdoudna.
Finally, I should mention that a two-act play named Gene Play, about the story of recDNA and CRISPR-Cas9, will be read by a cast of actors at the Vineyard Playhouse on June 19.
Excerpt from:
Science and Scientists on the Vineyard: Genes at play with CRISPR - Martha's Vineyard Times
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